CRYSTAL STRUCTURE AND PEPTIDE INHIBITORS OF HAUSP DEUBIQUITINASE
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United States of America Patent
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Issued Date -
Dec 12, 2013
app pub date -
Feb 22, 2012
filing date -
Feb 22, 2011
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Abandoned
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Abstract
Two vIRF4 (Kaposi's-sarcoma-associated-herpesvirus vIRF4) peptides, vif1, corresponding to aa202-216 of vIRF4, and vif2, corresponding to aa220-236 of vIRF4, are potent and selective HAUSP antagonists. The vif1 and vif2 peptides robustly suppress HAUSP DUB enzymatic activity, ultimately leading to p53-mediated anti-cancer activity. The vif1 and vif2 peptides, along with their homologues, are useful in treating cancer through regulation of p53 activity in a cancer cell. Also disclosed is the crystalline structure of vIRF4-HAUSP TRAF domain complex. The structure is useful in computer aided drug design for identifying an agent that interacts with and inhibits HAUSP, resulting in p53 medicated cell cycle arrest of cancer cells.
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